Breast cancer brain metastases show increased levels of genomic aberration-based homologous recombination deficiency scores relative to their corresponding primary tumors

Diossy, M; Reiniger, L [Reiniger, Lilla (Neuropatológia), author] I. Department of Pathology and experimental Can... (SU / FM / I); MTA-SE-NAP B Brain Metastasis Research Group (SU / FM / I / IIDP); Sztupinszki, Z [Sztupinszki, Zsófia (onkológia), author] II. Department of Pediatrics (SU / FM / C); Krzystanek, M; Timms, K M; Neff, C; Solimeno, C; Pruss, D; Eklund, A C; Tóth, E [Tóth, Erika (patológia), author] National Institute of Oncology; Kiss, O; Rusz, O [Rusz, Orsolya (onkológia), author] Department of Oncotherapy (USZ / ASZMS); Cserni, G [Cserni, Gábor (Patológia), author] Department of Pathology (USZ / ASZMS); Zombori, T [Zombori, Tamás (pathologia), author] Department of Pathology (USZ / ASZMS); Székely, B [Székely, Borbála (patologia), author] II. Department of Pathology (SU / FM / I); Tímár, J [Tímár, József (Rákkutatás, dagan...), author] II. Department of Pathology (SU / FM / I); Csabai, I [Csabai, István (Statisztikus fizika), author] Department of Physics of Complex Systems (ELTE / ELU FoS / Inst_Phys); Szallasi, Z ✉ [Szállási, Zoltán (Onkológia, dagana...), author] MTA-SE-NAP B Brain Metastasis Research Group (SU / FM / I / IIDP)

English Scientific Article (Journal Article)
Published: ANNALS OF ONCOLOGY 0923-7534 1569-8041 29 (9) pp. 1948-1954 2018
  • SJR Scopus - Hematology: D1
Identifiers
BackgroundBased on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor.Patients and methodsWe used a previously published next generation sequencing dataset of 21 matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also carried out the myChoice HRD analysis on an independent cohort of 17 breast cancer patients with matched primary/brain metastasis pairs.ResultsAll of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort, the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria.ConclusionsThe consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.
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2021-11-30 10:07